The ionic channels underlying electrical excitability in nerve and muscle membranes will be studied at the molecular level. The techniques will include voltage clamp on myelinated nerve or skeletal muscle fibers of frog for measuring ionic current, gating current and fluctuations of ionic current. The ionic currents carried by individual channels will be recorded from cultured neuroblastoma cells or myoballs. The gating kinetics of single Na and K channels will be analyzed. The relation between Na activation and gating current will be studied when the inactivaiton is slowed by toxin treatment or chemical modification. The individual and cooperative effects of different classes of neurotoxins on the individual Na channel will be investigated.